腺病毒载体携外源基因转染人培养静脉的实验研究

目的 :探讨经腺病毒载体介导的标记基因转染人培养大隐静脉后 ,标记基因表达的效率、转染靶细胞表达时相。方法 :从临床手术患者取得大隐静脉后 ,浸于含AdCMV/LacZ或AdCMV的病毒液中 (5× 10 9pfu) ,孵育 1h ,将静脉剪成静脉片 ,分别培养 2 ,7,14d。对转基因静脉片进行组织学检查。结果 :腺病毒载体可有效地将标记基因 (LacZ基因 )转入培养大隐静脉。转染后 2d内皮细胞和外膜细胞即有表达 ,β 半乳糖苷酶组织化学染色可见胞核蓝染阳性细胞 ,7d时表达最高 ,持续表达到第 14d。对照大隐静脉无β 半乳糖苷酶表达。 结论 :腺病毒载体能高效转染人大隐静脉 ,其靶细胞以内皮细胞为主 ,外源性基因的表达至少维持 2周左右     

Differences in Health-Related Quality of Life and Treatment Preferences Among Black and White Patients with End-Stage Renal Disease

BACKGROUND: Relatively little is known about racial differences in health-related quality of life (HRQL) among patients receiving dialysis for end-stage renal disease (ESRD) or how such differences may relate to preferences for renal transplantation. METHODS: We surveyed 1392 patients, ages 18-54 approximately 10 months after they initiated dialysis in 4 regions of the United States. The HRQL measures analyzed were overall health, emotional health, physical activity, energy level, social activity, and effect of ESRD on daily life. We also examined whether the measures of HRQL were associated with patients' preferences for renal transplantation by race. RESULTS: After adjustment for socioeconomic and clinical characteristics, Black women and men reported better overall health than White women and men, respectively. Black women reported higher energy levels than White women, and Black men reported less negative effects of ESRD on daily life compared to White men. Black men with high levels of physical activity were less likely to be certain about preferring a transplant than White men with similar levels of physical activity. CONCLUSIONS: Black patients receiving dialysis reported better HRQL than White patients, even after controlling for potential confounders. Racial differences in preferences for renal transplantation among men may be associated with their levels of physical activity.     

脑损伤后高血糖对大鼠血-脑屏障通透性的影响

目的 :研究脑损伤后高血糖对大鼠血 脑屏障通透性的影响。方法 :雄性Wistar大鼠 4 0只 ,随机分为 4组 :正常对照组 (Ⅰ组 ) ,高血糖组 (Ⅱ组 ) ,脑损伤后正常血糖组 (Ⅲ组 ) ,脑损伤后高血糖组 (Ⅳ组 )。应用流体冲击装置制作大鼠脑损伤模型 ,然后分别对高血糖及正常血糖组的血 脑屏障结构的损伤的标记物伊文蓝含量进行测定。结果 :在相同脑损伤的情况下 ,高血糖组的伊文蓝含量明显高于正常血糖组 (P <0 .0 1) ;同时以上 2组的伊文蓝含量均高于正常对照组及高血糖组 (无脑损伤组 ,P <0 .0 0 1) ;而正常对照组与高血糖组的伊文蓝含量无明显差异 (P >0 .0 5 )。结论 :脑损伤后高血糖使大鼠血 脑屏障通透性增高     

重度妊娠高血压综合征患者脑灌注压变化及其临床意义

目的 :通过检测重度妊娠高血压综合征 (妊高征 )脑灌注压变化 ,探讨脑灌注压变化与头痛症状的关系。方法 :选择重度妊高征 6 9例为实验组 ,正常晚期妊娠妇女 10 0例为对照组 ,采用Aaslid评估脑灌注压方法检测脑灌注压 ,评价妊高征患者脑灌注压变化及与头痛症状的关系。结果 :重度妊高征患者中异常脑灌注压患者明显多于正常脑灌注压患者 (P <0 .0 5 )。严重头痛和轻中度头痛患者脑灌注压均异常 ,且均以脑灌注压增高为多 (P<0 .0 5 )。在脑灌注压增高组中 ,严重头痛组脑灌注压明显高于轻中度头痛组 (P <0 .0 5 ) ;而在脑灌注压减低组中 ,严重头痛组脑灌注压又显著低于轻中度头痛组和无头痛症状组 (P <0 .0 5 )。 3组重度妊高征间平均动脉压比较无显著差异 (P >0 .0 5 )。无头痛症状组有脑灌注压正常和脑灌注压轻度降低 2种状态。结论 :高脑血流灌注状态和低脑血流灌注状态均可导致妊高征脑损害。高脑灌注压和低脑灌注压均是妊高征患者头痛发生的病理生理机制。高脑灌注压是妊高征头痛症状的主要原因 ,高脑灌注压患者更有发生子痫的危险     

A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function

Dietary protein restriction has been reported to delay the need for renal replacement therapy in clinical trials and meta-analyses. However, less clear is what effect dietary protein has on the rate of decline in renal function. We pooled the results of 13 randomized controlled trials (n = 1,919 patients) and found that dietary protein restriction reduced the rate of decline in estimated glomerular filtration rate by only 0.53 mL/min/yr (95% confidence interval [CI], 0.08 to 0.98 mL/min/yr). We also used weighted regression analysis to determine the reasons for the differences in the results of these 13 randomized trials along with 11 other nonrandomized controlled trials (n = 2,248 patients). The effect of dietary protein restriction (glomerular filtration rate decline in treatment minus control) was substantially less in randomized versus nonrandomized trials (regression coefficient, -5.2 mL/min/yr; 95% CI, -7.8 to -2.5 mL/min/yr; P < 0.05) and relatively greater among diabetic versus nondiabetic patients (5.4 mL/min/yr; 95% CI, 0.3 to 10.5 mL/min/yr; P < 0.05), while there was a trend toward a greater effect with each additional year of follow-up (2.1 mL/min/yr; 95% CI, -0.05 to 4.2 mL/min/yr; P = NS). However, the number of diabetic patients studied was small and the duration of follow-up was short in most trials. No other patient or study characteristics altered the effect of dietary protein restriction on the rate of decline in renal function. Thus, although dietary protein restriction retards the rate of renal function decline, the relatively weak magnitude of this effect suggests that better therapies are needed to slow the rate of renal disease progression.     

Autophagy contributes to BMP type 2 receptor degradation and development of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure which almost invariably leads to right heart failure and premature death. More than 70% of familial PAH and 20% of idiopathic PAH patients carry heterozygous mutations in the bone morphogenetic protein (BMP) type 2 receptor (BMPR2). However, the incomplete penetrance of BMPR2 mutations suggests that other genetic and environmental factors contribute to the disease. In the current study, we investigate the contribution of autophagy in the degradation of BMPR2 in pulmonary vascular cells. We demonstrate that endogenous BMPR2 is degraded through the lysosome in primary human pulmonary artery endothelial (PAECs) and smooth muscle cells (PASMCs): two cell types that play a key role in the pathology of the disease. By means of an elegant HaloTag system, we show that a block in lysosomal degradation leads to increased levels of BMPR2 at the plasma membrane. In addition, pharmacological or genetic manipulations of autophagy allow us to conclude that autophagy activation contributes to BMPR2 degradation. It has to be further investigated whether the role of autophagy in the degradation of BMPR2 is direct or through the modulation of the endocytic pathway. Interestingly, using an iPSC-derived endothelial cell model, our findings indicate that BMPR2 heterozygosity alone is sufficient to cause an increased autophagic flux. Besides BMPR2 heterozygosity, pro-inflammatory cytokines also contribute to an augmented autophagy in lung vascular cells. Furthermore, we demonstrate an increase in microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) levels in lung sections from PAH induced in rats. Accordingly, pulmonary microvascular endothelial cells (MVECs) from end-stage idiopathic PAH patients present an elevated autophagic flux. Our findings support a model in which an increased autophagic flux in PAH patients contributes to a greater decrease in BMPR2 levels. Altogether, this study sheds light on the basic mechanisms of BMPR2 degradation and highlights a crucial role for autophagy in PAH. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

The influence of physicians' practice management strategies and financial arrangements on quality of care among patients with diabetes

CONTEXT: Health care organizations use many strategies to influence physician behavior and the care delivered, but the effect of such strategies on quality is not known. OBJECTIVE: We sought to assess the influence of practice management strategies and financial arrangements on the quality of diabetes care. DESIGN: This was a retrospective cohort study including medical record reviews and a physician survey. PARTICIPANTS: Patients with diabetes mellitus (n=652) enrolled in 3 health plans located in Minnesota and 399 physicians in 135 practices who cared for them participated in this study. MAIN OUTCOME MEASURE: Our main outcome measures was a quality score indicating receipt of care in accordance with 6 accepted quality indicators. RESULTS: The mean quality score was 2.4 (SD 1.2) on a 6-point scale. Only a small proportion of the variation in quality was attributed to characteristics of physicians' practices (5%). Quality scores tended to be higher for patients whose physicians received quality performance reports or utilization profiles from more than 1 source (P=0.08), routinely enrolled diabetic patients in disease-management programs (P=0.06), or received diabetes-specific reports (P=0.06). Quality scores were lower for patients whose physicians were paid according to fee-for-service compared with salary (P=0.04) and served as gatekeepers for >50% of their patients (P=0.06). However, these findings were all of borderline statistical significance, and the absolute differences in quality were small. CONCLUSIONS: Current practice management strategies and financial arrangements have a limited impact on the quality of care for patients with diabetes. These findings suggest that other strategies may be necessary for health care organizations to improve care for patients with diabetes.     

生物黏附材料壳聚糖的黏附性能

目的:考察壳聚糖与黏蛋白的相互作用,评价壳聚糖黏附性能的影响因素。方法:于2006-07/12在中国科学院大连化学物理研究所生物医用材料工程实验室完成。将壳聚糖溶液与黏蛋白溶液混合,用紫外分光光度计测定溶液混合前后紫外吸收值的变化,表征壳聚糖的黏附性能。①调节反应溶液的pH值(1.0,3.0,5.0),考察环境pH对壳聚糖黏附性能的影响。②改变反应温度(4,25,37℃),考察环境温度对壳聚糖黏附性能的影响。③选择不同相对分子质量(48000,124000,230000)的壳聚糖,考察壳聚糖相对分子质量对其黏附性能的影响。④选择不同脱乙酰度(56%,67%,97%)的壳聚糖,考察壳聚糖脱乙酰度对其黏附性能的影响。⑤使用不同种类(I-S型及Ⅲ型)黏蛋白,考察黏蛋白中唾液酸含量对壳聚糖黏附性能的影响。结果:①环境介质pH由1.2升至5.0时,壳聚糖黏附性能随之显著升高。②壳聚糖黏附性能随着温度的升高而显著增强。③壳聚糖相对分子质量对于壳聚糖黏附无显著影响。④壳聚糖脱乙酰度增加,其黏附性能显著增强。⑤I-S型黏蛋白与壳聚糖的作用较之Ⅲ型黏蛋白与壳聚糖的相互作用明显增强。结论:壳聚糖的黏附受环境pH、温度、壳聚糖及黏蛋白两种分子电荷密度的显著影响;在酸性环境下增大环境pH值、升高环境温度、增加壳聚糖的脱乙酰度和增加黏蛋白中唾液酸的含量,均有利于壳聚糖的黏附。